Manufacture of 1,1-disubstituted-4,4-bipyridylium salts

ABSTRACT

A process for the manufacture of a 1,1&#39;&#39;-disubstituted-4,4&#39;&#39;bipyridylium salt which comprises reacting the corresponding Nsubstituted pyridinium salt with cyanamide ions, for example provided by an alkali metal cyanamide, and subsequently oxidising the resulting interaction product, for example by means of an oxidising agent which is an electron acceptor and which has a redox potential in water more positive than -0.50 volt as compared with the saturated calomel electrode.

United States Patent [191 Carey Aug. 28, 1973 MANUFACTURE OF 1,1-DlSUBSTITUTED-4,4-BIPYRIDYLIUM SALTS Inventor: John Gerard Carey,Runcom,

England Imperial Chemical Industries Limited, London, England Filed:Oct. 20, 1970 Appl. No.: 82,503

Assignee:

Foreign Application Priority Data Oct. 27, 1969 Great Britain 52,450/69US Cl. 260/295 Q, 260/296 D, 260/247.2,

260/247.5, 260/293.63, 260/293.69, 71/82 Int. Cl C07d 31/32 Field ofSearch 260/296 D, 295 Q References Cited UNITED STATES PATENTS 8/1967Downes et a1. 260/296 D 3,405,135 10/1968 Colchester et al 260/296 DPrimary Examiner-Henry R. Jiles Assistant Examiner-Robert T. BondAttorneyCushman, Darby & Cushman l 5 ABSTRACT 12 Claims, No DrawingsMANUFACTURE OF 1 ,l -DISUBSTITUTED-4,4-BIPYRIDYLIUM SALTS This inventionrelates to the manufacture of 1,1.- disubstituted-4,4-bipyridylium saltswhich are useful herbicides.

According to the present invention we provide a process for themanufacture of a l,l-disubstituted-4,4- bipyridylium salt whichcomprises reacting the corresponding N-substituted pyridinium salt withcyanamide ions and subsequently oxidising the resulting interactionproduct.

The cyanamide ions (HC=C=N may be provided by a wide range ofcyanamides, including metal and especially alkali metal cyanamides forexample sodium cyanamide.

The reaction can be carried out simply by mixing the reagents andheating the mixture if necessary, but we prefer to carry out thereaction in a solvent for the N- substituted pyridinium salt. It ispreferred to use a polar aprotic solvent, for example acetone, amidesand particularly tertiary alkyl amides (for example dimethylformamide),sulphoxides (for example dimethylsulphoxide), sulphones (for examplesulpholane), nitriles (for example acetonitrile), nitro compounds (forexample nitropropane), and alkyl carbonates (for example propylenecarbonate). Mixtures of solvents may be used if desired.

The temperature at which the reaction is carried out is not criticalalthough in some cases it is advantageous to heat the reaction mixture.In general the reaction may be carried out at a temperature from 25C to120C, preferably from 40C to 90C. Temperatures above 150C should ingeneral be avoided. Usually the reaction will be carried out under aninert atmosphere.

The reaction is preferably carried out under basic conditions and it maybe carried out in the presence of an added base. A strong base (ifpresent) is preferred, for example an alkali metal hydroxide, althoughammonium hydroxide or an organic amine may be used. In polar aproticsolvents, for example anhydrous dimethyl sulphoxide the addition of aseparate base may not be essential since the cyanamide itself may besufficiently basic under thereaction conditions. A separate base may,however, be added in such cases if desired.

The amount of the cyanamide is not critical although we prefer to employan excess of cyanamide ions. Preferably at least 0.25 mole of thecyanamide ions is used per mole of the N-substituted pyridinium salt.The concentration of the pyridinium salt in cases where it is employedin the form of a solution will depend upon the particular solvent used;the optimum concentration in each case can be determined by simpleexperiment. In general, however, concentrations of from 0.1 to 2.0 molesper litre and especially about 0.5 mole per litre are suitable.

Any N-substituted pyridinium salt may be converted to the correspondingl,l '-disubstituted-4,4'- bipyridylium salt by the process of theinvention and particularly suitable salts are those having an alkyl or acarbamidoalkyl substituent on the nitrogen atom of the pyridine nucleus.The carbamidoalkyl substituent has the formula R,CO-NR,R wherein R is ahydrocarbon radical (especially the methylene radical) and R, and R arehydrocarbon or substituted hydrocarbon radicals and R, and R, may,together with the attached nitrogen atom make up a heterocyclic ring forexample an optionally substituted piperidine or morpholine ring. Thesalt is conveniently a halide and especially the chloride salt, thoughthe anionic species is not critical and pther salts for example themethosulphate may be used, if desired. The pyridine nucleus may besubstituted, for example by one or more alkyl groups in the 2, 3, 5 and6 positions, but the 4-position preferably should be unoccupied. In thecase of an N-alkyl pyridinium salt the alkyl group preferably containsfrom one to four carbon atoms. Similarly where the groups R and R arealkyl groups these preferably contain from 1 to 4 carbon atoms.

The interaction product derived from the pyridinium salt and thecyanamide ions is a l,l-disubstituted l,l-dihydro-4,4-bipyridyl which isreadily oxidised to the corresponding l,l-disubstituted-4,4-bipyridylium salt by treatment with an oxidisingagent which is an electron acceptor and which has a redox potential inwater more positive than 0.50 volt as compared with the saturatedcalomel electrode. Examples of suitable oxidising agents are cericsulphate (in dilute sulphuric acid); metal salts, especially thehalides; inorganic oxyacid anhydrides, especially sulphur dioxide;chlorine; air or oxygen, preferably in conjunction with water and/orcarbon dioxide and/or an acid for example acetic acid or sulphuric acid;and organic oxidising agents for example quinones such as benzoquinone,chloranil and anthraquinone. The oxidation is advantageously carried outunder acidic conditions, the apparent pH of the reaction mixture beingpreferably less than 6, especially from 4 to 6. Addition of theoxidising agent in an acidic medium is usually sufficient to achievethis result. A wide range of temperatures, for example from 0C to C maybe employed for the oxidation step.

Depending upon the conditions under which it is prepared thel,l'-disubstituted dihydrobipyridyl interaction product may be in theform of a solution or a slurry.

The l,l'-disubstituted dihydrobipyridyl can be oxidised directly withoutisolation from the mixture in which it has been prepared but it isusually more convenient to isolate the intermediate reaction productprior to oxidising it so that oxidation yields a fairly purebipyridylium salt. In the case where the intermediate product is aslurry the solid can be isolated by filtration or preferably by solventextraction. Suitable solvents forthe extraction are hydrocarbons,especially aromatic hydrocarbons and notably toluene. The temperature ofthe extraction can be from 0C to 100C.

In the case where the intermediate reaction product is in solution, asfor example when it is prepared in a polar aprotic solvent, we havefound that a useful technique for isolating it is to add water or anacid, eg an organic acid, notably acetic acid, to the reaction mixture.The temperature of this treatment can be from 0C to 100C, preferablyfrom 20C to 50C. The solid and liquid phases of the slurry so obtainedcan be treated as described above to recover the intermediate reactionproduct.

l,l '-disubstituted-4,4'-bipyridylium cations may conveniently beseparated from the anions in the final reaction mixture by treating themixture with 4,4- diamino-stilbene-2,2'-disulphonic acid which iscommonly known as amsonic acid. The bipyridylium cation is therebyprecipitated from the mixture in the form of its amsonate salt whilstthe anions remain in the mixture. The precipitate can then be removed byfiltration, washed and dried in conventional manner and the amsonic acidcan be regenerated and recovered for re-use by acidification of theamsonate salt, preferably employing an aqueous solution of the acid. Theacid used to recover the amsonic acid can be selected so as to providethe desired anion for the resulting bipyridylium salt and can be forexample hydrochloric acid, phosphoric acid or acetic acid.

Amsonic acid is only sparingly soluble in water and it is thereforeusually employed in the present invention in the form of an aqueoussolution of one of its watersoluble salts, conveniently an alkali metalsalt or the ammonium salt. The treatment of the reaction mixture withamsonic acid can be conveniently at a pH in the range 7 to 12, and at atemperature of from C to 100C.

The l,1'-disubstituted-4,4-bipyridylium cation can also be separatedfrom the anions in the reaction mixture by contacting this mixture'witha suitable cationexchange resin. In this way the anions pass through theresin and remain in the mixture so that they are separated from thebipyridylium cation. The bipyridylium cation can subsequently beliberated from the ionexchange resin by treatment of the resin with anacid. In this way a bipyridylium salt is obtained wherein the anion isthat supplied by the acid. Examples of the anions which may beintroduced into mixture in this way are chloride, sulphate and acetateions.

The temperature at which the mixture is contacted with the ion-exchangeresin is not critical but can conveniently be from 0C to 100C. Examplesof suitable cation-exchange resins are Zeocarb cation exchange resins,for example Zeocarb 225 (SRC -8), the Amberlite cation exchange resinsfor example Amberlite Resin C6-120, and the Deacidite resins.

The invention is illustrated but in no way limited by the followingexamples.

. EXAMPLE 1 N-methyl pyridinium chloride (0.01 mole) was added withstirring a solution of sodium cyanamide (0.02 mole) in dimethylsulphoxide (30 ml) at 70C under an atmosphere of nitrogen. The solutionbecame dark brown in colour. After 2% hours a cooled solution of sulphurdioxide in dimethyl sulphoxide was added to the reaction mixture. Excesssulphur dioxide was then EXAMPLE 2 The procedure of Example 1 wasrepeated using N- (N-dimethyl-carbamidomethyl)-pyridinium chlorideinstead of N-methyl pyridinium chloride. The product was1,1-di(N-dimethyl carbamidomethyl )-4,4- bipyridylium ion and thereaction efficiency was 20 percent based on pyridinium salt fed.

I claim:

1. A process for the manufacture of a 1,1-disubstituted-4,4-bipyridylium salt wherein the 1,1- substituents areselected from alkyl of one to four carbon atoms and carbamidoalkyl ofthe formula -R,CONR,R wherein R is the methylene radical, R and R arealkyl groups of one to four carbon atoms and R and R may, together withthe attached nitrogen atom, make up a piperidine or morpholine ringwhich comprises reacting in a polar aprotic solvent at temperatures from25C to 120C at least 0.1 moles per litre of the correspondingN-substituted pyridylium salt with cyanamide ions under basic conditionsto form a 1,1 -di-substituted-1 ,1 -dihydro-4,4-bipyridyl andsubsequently treating the dihydrobipyridyl with an oxidising agent whichis an electron acceptor and which has a redox potential in water morepositive than -O.50 volt as compared with the saturated calomelelectrode to form the 1,1'-disubstituted-4,4'-bipyridylium salt.

2. A process as claimed in claim 1 wherein the cyanamide ions areprovided by an alkali metal cyanamide.

3. A process as claimed in claim 1 wherein the reaction is carried outat a temperature of from 40C to C.

4. A process as claimed in claim I wherein the reaction is carried outin the presence of an added base.

5. A process as claimed in claim 1 wherein at least 0.25 mole ofcyanamide ions is employed per mole of the N-substituted pyridiniumsalt.

6. A process as claimed in claim 1 wherein the concentration of theN-substituted pyridinium salt. is from 0.1 to 2 moles per litre.

7. A process as claimed in claim 1 wherein the oxidation is carried outunder acidic conditions.

8. A process as claimed in claim 1 wherein the interaction mixture isisolated prior to oxidation from the reaction mixture in which it hasbeen prepared.

9. A process as claimed in claim 8 wherein the interaction product is insolution and is precipitated by adding water or acid to the reactionmixture.

10. A process as claimed in claim 8 wherein the interaction product isisolated by solvent extraction.

ll. A process as claimed in claim 1 wherein the 1,1- substituents 0f the1,1 '-disubstituted-4,4'-bipyridylium salt are carbamidomethyl groups.

12. A process as claimed in claim 10 wherein each alkyl group is themethyl group.

2. A process as claimed in claim 1 wherein the cyanamide ions areprovided by an alkali metal cyanamide.
 3. A process as claimed in claim1 wherein the reaction is carried out at a temperature of from 40*C to90*C.
 4. A process as claimed in claim 1 wherein the reaction is carriedout in the presence of an added base.
 5. A process as claimed in claim 1wherein at least 0.25 mole of cyanamide ions is employed per mole of theN-substituted pyridinium salt.
 6. A process as claimed in claim 1wherein the concentration of the N-substituted pyridinium salt is from0.1 to 2 moles per litre.
 7. A process as claimed in claim 1 wherein theoxidation is carried out under acidic conditions.
 8. A process asclaimed in claim 1 wherein the interaction mixture is isolated prior tooxidation from the reaction mixture in which it has been prepared.
 9. Aprocess as claimed in claim 8 wherein the interaction product is insolution and is precipitated by adding water or acid to the reactionmixture.
 10. A process as claimed in claim 8 wherein the interactionproduct is isolated by solvent extraction.
 11. A process as claimed inclaim 1 wherein the 1,1''-substituents of the1,1''-disubstituted-4,4''-bipyridylium salt are carbamidomethyl groups.12. A process as claimed in claim 10 wherein each alkyl group is themethyl group.